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Title: Lipidomic changes in rat liver after long-term exposure to ethanol

Abstract

Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrarymore » to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. - Highlights: > Long term exposure to ethanol was studied. > A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. > We examined the clustering pattern of the NMR data with principal component analysis. > NMR data were compared with histology and immunohistochemistry data. > Biochemical parameters were compared with the observed NMR lipid data.« less

Authors:
;  [1];  [2];  [1];  [1];  [3]
  1. Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555 (United States)
  2. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555 (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
21587829
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 255; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2011.05.022; PII: S0041-008X(11)00240-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MARKERS; CARBOXYLIC ACIDS; DISEASE INCIDENCE; DISEASES; ETHANOL; INFLAMMATION; LECITHINS; LIVER; MALTOSE; MORTALITY; NUCLEAR MAGNETIC RESONANCE; OXIDATION; PHOSPHORUS; PLASMA; RATS; SPECTROSCOPY; TIME DEPENDENCE; TRIGLYCERIDES; ALCOHOLS; ANIMALS; BODY; CARBOHYDRATES; CHEMICAL REACTIONS; DIGESTIVE SYSTEM; DISACCHARIDES; ELEMENTS; ESTERS; GLANDS; HYDROXY COMPOUNDS; LIPIDS; MAGNETIC RESONANCE; MAMMALS; NONMETALS; OLIGOSACCHARIDES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PHOSPHOLIPIDS; RESONANCE; RODENTS; SACCHARIDES; SYMPTOMS; VERTEBRATES

Citation Formats

Fernando, Harshica, Bhopale, Kamlesh K., Kondraganti, Shakuntala, Kaphalia, Bhupendra S., Shakeel Ansari, G.A., E-mail: sansari@utmb.edu, and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555. Lipidomic changes in rat liver after long-term exposure to ethanol. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.05.022.
Fernando, Harshica, Bhopale, Kamlesh K., Kondraganti, Shakuntala, Kaphalia, Bhupendra S., Shakeel Ansari, G.A., E-mail: sansari@utmb.edu, & Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555. Lipidomic changes in rat liver after long-term exposure to ethanol. United States. doi:10.1016/j.taap.2011.05.022.
Fernando, Harshica, Bhopale, Kamlesh K., Kondraganti, Shakuntala, Kaphalia, Bhupendra S., Shakeel Ansari, G.A., E-mail: sansari@utmb.edu, and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555. 2011. "Lipidomic changes in rat liver after long-term exposure to ethanol". United States. doi:10.1016/j.taap.2011.05.022.
@article{osti_21587829,
title = {Lipidomic changes in rat liver after long-term exposure to ethanol},
author = {Fernando, Harshica and Bhopale, Kamlesh K. and Kondraganti, Shakuntala and Kaphalia, Bhupendra S. and Shakeel Ansari, G.A., E-mail: sansari@utmb.edu and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555},
abstractNote = {Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. - Highlights: > Long term exposure to ethanol was studied. > A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. > We examined the clustering pattern of the NMR data with principal component analysis. > NMR data were compared with histology and immunohistochemistry data. > Biochemical parameters were compared with the observed NMR lipid data.},
doi = {10.1016/j.taap.2011.05.022},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 255,
place = {United States},
year = 2011,
month = 9
}
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